1. Field of the Invention
The present invention relates to a method and device for accurately handling and delivering infinitesimal amounts of fluid in an elastic polymeric substrate of microfluidic devices used in chemical and biochemical analyses, syntheses and detection. The method and device deliver fluid in microchannels formed within an elastic polymeric substrate by using a rotor to apply external force onto the elastic polymeric substrate so that the fluid in the microchannels is forced therethrough.
2. Description of the Background Art
As science and technology develops, interest about component miniaturization and process automation is increasing. Miniaturization reduces the size and weight of an apparatus and reduces the amount of electricity needed for its operation, resulting in the development of portable experimental equipment, such as microfluidic devices. Also, the amount of samples or reagents needed for experiments is substantially reduced and accordingly, experiments using costly samples or reagents can be conducted more efficiently. By automation, a number of processes in conducting experiments can be conducted automatically not by manual labor but by mechanical means. Generally, experiments conducted in laboratories are mainly conducted by performing respective independent processes in parallel or in order. Such processes may require much labor and time. Accordingly, continuity and efficiency are reduced and inaccuracy of experiments increases. Therefore, if automation of experiments is achieved, continuity and efficiency of the experiments are increased, thus the required labor and time can be minimized while accuracy of the experiments is improved.
As micromachining develops together with semiconductor technology, research to achieve miniaturization and automation simultaneously is in process. As an example of such research, the so-called xe2x80x9cLab-on-a-chipxe2x80x9d has been developed. Lab-on-a-chip is a chemical microprocessor made by integrating many kinds of apparatuses on a substrate (chip) having a dimension of several centimeters being made of glass, silicone or plastic using photolithography or micromachining used generally in semiconductor technology, and allows automated experiments to be conducted with high speed, high efficiency and low cost (Kovas, Anal. Chem. 68 (1996) 407A-412A). By miniaturizing and integrating many apparatuses onto a chip needed for experimentation and by automating the respective experiment processes to be conducted consecutively, experiments can be conducted more efficiently. Recently, as a result of new technological advances, satisfactory results in developing new medicines and new materials have been obtained by searching, through hundreds of thousands of chemical compound libraries to yield an approach for probable problem-solving solutions. Accordingly, research for compiling and analyzing chemical compound libraries using combinatorial chemical methods are being conducted. To conduct such research, trials to develop experimental methods for synthesizing or analyzing various kinds of samples using a lab-on-a-chip enabling high speed, high efficiency, low cost, miniaturization and automation, are in progress.
As miniaturization and automation are progressed, necessity of new technologies is on the rise because conventional methods used to handle and deliver solutions can not be applied appropriately to provide the necessary infinitesimal amounts of solution transfer needed for experiments. Conventional methods for delivering solutions are inappropriate for delivering infinitesimal amounts of solution due to many factors such as minimum delivery amount or delivery conditions. Also, factors which are not problematic in delivering large amounts of solution may cause serious problems when delivering infinitesimal amounts of solution. For example, due to surface tension generated between the delivered solution and the inner walls of the microchannels upon fluid transfer therethrough, the solution can be delivered in an unexpected direction or delivered inefficiently. Also, due to an increase in the so-called xe2x80x9cback pressurexe2x80x9d generated when the solution flows in the microchannel, pressure for delivery increases undesirably, and accurate amount of delivery is difficult because portions of the solution may vaporize in the microchannel.
As a method to deliver infinitesimal amounts of solution in a microchannel, the most common method employs electric fields. The method of using electric fields can control the flow of solution by using capillary electric osmosis generated when a voltage is applied at both ends of the microchannel filled with the solution without using an additional pump or valve. It is also possible to analyze samples on the chip because separation of the sample using capillary electrophoresis is possible (Harrison, Science 261 (1993) pp.895-897; Jacobson, Anal. Chem. 66 (1994) pp.4127-4132; Li, Anal. Chem. 69 (1997) pp.1564-1568; Kopp, Science 280 (1998) pp.1046-1048). The apparatus for this method is simple and accordingly, this method is used most commonly in the field of delivering solutions in microchannels such as those in a lab-on-a-chip. However, if one or more channels are connected in a complicated manner, controlling the delivery of the solution is difficult. Accurate delivery is also difficult or impossible if various kinds of solutions are delivered because the flow rate of the solution is affected by the physical properties, such as acidity (pH), ionic strength and viscosity, of the solution to be delivered and microchannel surface condition.
In addition to the above method, much research has been conducted to develop a method for accurately delivering an infinitesimal amounts of solution for microfluidic devices. First, there is a method for delivering a solution by connecting an external micropump to a microchannel. For this method, a peristaltic pump, injector pump or HPLC pump is used, or a method using compressed air is also applied (Hosokawa, Anal. Chem. 72(1999) pp.7481-4785). However, such methods can only deliver solutions in the amount of microliters and accordingly, they are inappropriate for many fields such as the lab-on-a-chip technique, which handle and deliver infinitesimal amounts of solution in the level of nanoliters or picoliters. Also, waste of unnecessary reagents or samples is increased since the fluid must be filled from the pump to the microchannels to connect the external micropump with the microchannels of the lab-on-a-chip. Also, the fluid can leak from the portion connecting the chip and the external micropump since the pressure for delivering the solution is undesirably generated at the external portions of the chip and accordingly, complicated and sophisticated design and assembly are necessary.
Research of various techniques to deliver a solution by directly embodying a micropump in a chip are actively pursued, to overcome disadvantages in the method of connecting an external micropump with a microchannel in the chip. As the result of such research, many methods were reported, including a method of using piezoelectric material having a diaphragm in the chip (Andersson, Sens. Actuators B72(2001) pp.259-265; Nguyen, Sens. Actuator A (2001), pp.104-111), an on chip-type diaphragm pump for delivering the solution by vibrating the diaphragm using air pressure (Scomburg, J. Micromech. Microeng. 3(1993) pp.216-218), a method for delivering the solution by making air bubbles in the microchannel through a electrochemical reaction therein (Bohm, Proceedings of the Transducers, Sendai, Japan, 1999. pp.880-881) and the like. However, to accommodate such methods, manufacturing an appropriate chip structure is difficult since additional elements or devices must be embodied to deliver the solution in the chip. Also, conventional devices such as electroosmotic pump are inappropriate for delivering various kinds of solutions because the physical properties of the delivered solutions affect accurate fluid delivery.
Therefore, the present invention provides a method and device for handling and delivering fluid in an elastic polymeric substrate, and for delivering various kinds of fluids in an infinitesimal amount in the range from picoliters to milliliters at a constant rate regardless of the physical properties of the fluid in the substrate having a microchannel therein. Additional external devices or structures on the substrate are not required to handle and deliver the fluid.
A gist of the present invention involves the identification of conventional art problems related to handling and delivering accurate and infinitesimal amounts of fluid through microchannels. In one embodiment, the present invention solves such problems by periodically applying an external (mechanical) force onto a polymeric substrate using a rotor to compress the microchannel having fluid therein, and periodically releasing the applied external force from the substrate to decompress the microchannel like peristaltic pump to deliver fluid therethrough.
In other words, in accordance with the present invention, a fluid is transferred through the microchannel by periodically squeezing selective portions thereof, and a chemical operation is performed by using the transferred fluid.
The foregoing and other features, aspects and advantages of the present invention will become more apparent from the following detailed description when taken in conjunction with the accompanying drawings.